SynthesisFrontiers in endocrinology2026
Health-related quality of life and patterns of psychological vulnerability in autoimmune Addison's disease: a systematic review.
Synthesis in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Autoimmune primary adrenal insufficiency (PAI) is the most common cause of Addison's disease (AD) in Western countries and requires lifelong glucocorticoid and mineralocorticoid replacement. Despite biochemical control, many patients report persistent fatigue, functional limitations, and reduced well-being. However, evidence on health-related quality of life (HR-QoL) and psychopathological outcomes in autoimmune PAI remains fragmented and is often derived from mixed AD cohorts, limiting autoimmune-specific interpretation. This systematic review aimed to synthesise quantitative evidence on HR-QoL and psychological outcomes in adults with autoimmune PAI. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science from inception to February 2026 for English-language quantitative studies assessing HR-QoL and/or psychological outcomes in adults with autoimmune PAI or cohorts in which autoimmune aetiology of PAI was predominant. Study selection and data extraction were performed independently by two reviewers. Methodological quality was assessed using the NIH Study Quality Assessment Tools. The protocol was registered in PROSPERO (CRD420261322821). Results: Twenty-three studies met the inclusion criteria, including 1,764 participants with autoimmune PAI. Most investigations were observational, including eight cross-sectional and five case-control studies, while nine were interventional trials and one was a prospective observational study. HR-QoL was consistently reduced across studies, with the most prominent impairments observed in vitality, energy, and physical functioning domains. Female sex and greater autoimmune comorbidity were repeatedly associated with poorer perceived outcomes. Treatment-related findings were heterogeneous, with more consistent improvements observed in disease-specific HR-QoL following modified-release hydrocortisone or infusion strategies, while generic measures often showed limited change. Evidence on psychopathological symptoms was comparatively limited and mixed. Anxiety and depressive symptoms were generally mild and inconsistently elevated, while convergent findings emerged for mental fatigue, subjective executive functioning difficulties, and sexual distress in selected samples. Conclusions: Autoimmune PAI is associated with a persistent functional and psychological burden that is only partly captured by biochemical control. Integrating patient-reported outcomes into routine care may help identify individuals at risk of persistent impairment and support more comprehensive, multidisciplinary, patient-centred management strategies. Future longitudinal studies using harmonised outcome measures are needed to clarify trajectories, determinants, and potential targets for supportive interventions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261322821.
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